Distinct Immune Landscape and Gene Expression Profiles in Breast Cancer: Young versus Non-Young Patients

Breast cancer remains a prevalent malignancy worldwide, particularly affecting younger women more aggressively. Significant differences in clinical and biological characteristics exist between breast cancer with young patients (BCY) and breast cancer with non-young patients (BCNY). However, the role of the immune microenvironment in these differences is not fully understood.

Data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were analyzed to compare tumor-infiltrating immune cells (TIICs) and gene expression between BCY and BCNY. The CIBERSORT algorithm was used to estimate the relative abundance of 22 immune cell types, and differentially expressed genes were identified using the "limma" package in R.

The BCY group had a higher prevalence of M0 macrophages and activated dendritic cells, while the BCNY group exhibited greater infiltration of CD4 memory T cells, M2 macrophages, and neutrophils. Differential gene expression analysis identified 11 significantly expressed genes between the groups, with genes such as FDCSP and GABRP upregulated in the BCY group. GSEA revealed that pro-inflammatory pathways, such as cytokine-cytokine receptor interaction, were enriched in the BCY group, while pathways related to metabolism and extracellular matrix interactions were enriched in the BCNY group. Kaplan-Meier analysis demonstrated that high expression of certain genes, such as NAT1, CA12, and SRARP, was associated with better relapse-free survival.

This study reveals significant differences in immune cell infiltration, gene expression, and pathways between BCY and BCNY, providing insights into the aggressive tumor biology that may explain the poorer prognosis of BCY.